This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Perinatal asphyxia, defined as a severe lack of oxygen to the fetus during labor and delivery, remains a significant health problem, accounting for 23% of neonatal deaths worldwide. Up to 60% of survivors are left with severe and life-long neurodevelopmental handicaps that include mental retardation, cerebral palsy, seizures and learning disabilities. The goal of this research is to develop an approach to perinatal asphyxia that will decrease the neurologic injury sustained from lack of oxygen to the brain, thereby helping affected children achieve their full potential and lead healthy and productive lives. Both erythropoietin (Epo) and hypothermia are neuroprotective, improving short and long term neurologic outcome following brain injury in neonatal and adult animal models. Neither treatment is completely protective. We hypothesize that Epo combined with hypothermia will decrease the sequelae of perinatal asphyxia more than either therapy alone. We have established a model of perinatal asphyxia which enables testing of the efficacy and safety of a combined neuroprotective treatment strategy under conditions that closely resemble human neonatal emergencies. We will use this model to test the following specific aims: 1) to compare the efficacy of Epo or hypothermia alone, Epo with hypothermia, and placebo on the neurodevelopmental and structural sequelae of moderate perinatal asphyxia;2) to test the individual and combined safety of these treatments. Evaluation will include EEG, MRI, neurobehavioral evaluations, biochemical and immunohistochemical studies. This work will produce important data with direct clinical application directed towards substantially lessening the financial and emotional consequences of birth asphyxia.